Abstract
Lymphocyte cytosolic protein 2 (LCP2) is one of the SLP-76 family of adapters, which are critical intermediates in signal cascades downstream of several receptors. LCP2 regulates immunoreceptor signaling (such as T-cell receptors) and is also required for integrin signaling in neutrophils and platelets. However, the role of LCP2 in the tumor microenvironment is still unknown. In this study, we found a significant increase of mRNA and protein expression of LCP2 in metastatic skin cutaneous melanoma compared to normal skin. The upregulation of LCP2 was associated with good overall survival of patients with metastatic skin cutaneous melanoma, who received pharmacotherapy and radiation. GSEA signaling pathways analysis showed that LCP2 was involved in multiple pathways of immune response and correlation analysis revealed LCP2 was positively correlated with molecules in TCR signaling and 11 immune checkpoints, while LCP2 negatively correlated with 2 immune checkpoints in the metastatic skin cutaneous melanoma. According to the different expressions of LCP2, high LCP2 expression was positively correlated with more tumor-infiltrating CD8+ T cells. Furthermore, Kaplan–Meier plot indicated that LCP2 acted as a prognostic biomarker for progression-free survival of patients with metastatic skin cutaneous melanoma receiving anti-PD1 immunotherapy. In conclusion, our results integrated both the expression and function of LCP2 in melanoma using multiple tools, shedding light on the potential role of LCP2 in melanoma, and suggesting LCP2 serves as a prognostic biomarker and therapeutic target in anti-tumor immunity.
Highlights
Abbreviations lymphocyte cytosolic protein 2 (LCP2) Lymphocyte cytosolic protein 2 TCR T cell antigen receptor KIRC Kidney renal clear cell cancer KIRP Kidney renal papillary cell cancer skin cutaneous melanoma (SKCM)-Metastasis Skin cutaneous melanoma with metastasis STAD Stomach adenocarcinoma THCA Thyroid cancer BLCA Bladder cancer COAD Colon adenocarcinoma LIHC Liver hepatocellular cancer HNSC Head and neck squamous cell cancer LUAD Lung adenocarcinoma LUSC Lung squamous cell cancer
Our previous study indicated that lymphocyte cytosolic protein 2 (LCP2) protein tightly interacted with UBASH3B protein, which was identified as a novel prognostic biomarker and correlated with immune cell infiltration in the tumor m icroenvironment[6]
We found mRNA and protein of LCP2 was highly expressed in SKCM-Metastasis
Summary
Abbreviations LCP2 Lymphocyte cytosolic protein 2 TCR T cell antigen receptor KIRC Kidney renal clear cell cancer KIRP Kidney renal papillary cell cancer SKCM-Metastasis Skin cutaneous melanoma with metastasis STAD Stomach adenocarcinoma THCA Thyroid cancer BLCA Bladder cancer COAD Colon adenocarcinoma LIHC Liver hepatocellular cancer HNSC Head and neck squamous cell cancer LUAD Lung adenocarcinoma LUSC Lung squamous cell cancer. Tumor-infiltrating immune cells play essential roles in affecting disease prognosis and are indicators of anti-tumor responses in patients with metastatic melanoma receiving immune checkpoint inhibitors[2]. Our previous study indicated that lymphocyte cytosolic protein 2 (LCP2) protein tightly interacted with UBASH3B protein, which was identified as a novel prognostic biomarker and correlated with immune cell infiltration in the tumor m icroenvironment[6]. The function of LCP2 might vary from diseases, and further studies are required according to the gene profile alteration of immune cells in the tumor microenvironment. With this regard, deciphering the role of LCP2 in melanoma and the interaction between LCP2 and immune cells in melanoma will be of great interest. Understanding the complex interplay of LCP2 and the immune cells in melanoma could predict the therapeutic response of immune checkpointrelated therapy
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